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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Plazomicin: Drug information

Plazomicin: Drug information
(For additional information see "Plazomicin: Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: US Boxed Warning
Nephrotoxicity:

Nephrotoxicity has been reported with plazomicin. The risk of nephrotoxicity is greater in patients with impaired renal function, the elderly, and in those receiving concomitant nephrotoxic medications. Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy. Therapeutic Drug Monitoring (TDM) is recommended for complicated urinary tract infection (cUTI) patients with CrCl <90 mL/minute to avoid potentially toxic levels.

Ototoxicity:

Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, has been reported with plazomicin. Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of therapy. Aminoglycoside-associated ototoxicity has been observed primarily in patients with a family history of hearing loss, patients with renal impairment, and in patients receiving higher doses and/or longer durations of therapy than recommended.

Neuromuscular blockade:

Aminoglycosides have been associated with neuromuscular blockade. During therapy with plazomicin, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or in patients concomitantly receiving neuromuscular-blocking agents.

Pregnancy:

Aminoglycosides, including plazomicin, can cause fetal harm when administered to a pregnant woman.

Brand Names: US
  • Zemdri
Pharmacologic Category
  • Antibiotic, Aminoglycoside
Dosing: Adult

Note: Aminoglycoside dosing weight: For underweight patients (ie, total body weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For nonobese patients (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or IBW. TBW may be preferred in nonobese patients who may have increased Vd (eg, critically ill). For obese patients (ie, TBW >1.25 x IBW), use 40% adjusted body weight ([0.4 x {TBW-IBW}] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCl) (Asempa 2019; Pai 2014; Trang 2019; Traynor 1995).

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Reserve for patients with or at risk for resistant infections, including carbapenem-resistant Enterobacterales (IDSA [Tamma 2020]; Quale 2021).

Inpatients: IV: 15 mg/kg once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Connolly 2018; Hooton 2021; IDSA [Tamma 2020]; Wagenlehner 2019).

Outpatients: IV: 15 mg/kg once, followed by 5 to 14 days of appropriate oral therapy (Connolly 2018; Hooton 2021; IDSA [Tamma 2020]). Note: For patients who are systemically ill, at risk for more severe illness, or at risk for multidrug-resistant infection, some experts continue daily parenteral therapy pending culture and susceptibility testing results (Hooton 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

Note: CrCl estimated by Cockcroft-Gault formula using TBW (or IBW for patients with TBW ≥25% IBW)

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 30 to <60 mL/minute: 10 mg/kg every 24 hours

CrCl 15 to <30 mL/minute: 10 mg/kg every 48 hours

CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

End-stage renal disease (ESRD) requiring hemodialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Continuous renal replacement therapy (CRRT): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Note: For patients with CrCl ≥15 mL/minute to <90 mL/minute, measure plasma trough concentration within 30 minutes prior to second dose. If trough concentration is ≥3 mcg/mL, extend dosing interval by 1.5 fold (ie, from every 24 hours to 36 hours or from every 48 hours to 72 hours).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity: Adult

For patients with TBW greater than ideal body weight (IBW) by ≥25%, use 40% adjusted body weight (ABW) for dosing. ABW = IBW + 0.4 x (TBW-IBW).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as sulfate [preservative free]:

Zemdri: 500 mg/10 mL (10 mL)

Generic Equivalent Available: US

No

Administration: Adult

IV: Infuse over 30 minutes.

Use: Labeled Indications

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infections (UTI), including pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae in patients ≥18 years. Note: Reserve for use in complicated UTI patients who have limited or no alternative treatment options.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Hypertension (2%), hypotension (1%)

Central nervous system: Headache (1%)

Gastrointestinal: Diarrhea (2%), nausea (1%), vomiting (1%)

Genitourinary: Nephrotoxicity (4%)

Otic: Ototoxicity (2%)

Renal: Increased serum creatinine (4%; CrCl: 30 to 90 mL/minute: ≤10%), acute renal failure (≤4%), decreased creatinine clearance (≤4%), renal disease (≤4%), renal failure syndrome (≤4%), renal insufficiency (≤4%)

Frequency not defined:

Central nervous system: Dizziness

Endocrine & metabolic: Hypokalemia

Gastrointestinal: Constipation, gastritis

Genitourinary: Hematuria

Hepatic: Increased serum alanine aminotransferase

Respiratory: Dyspnea

<1%, postmarketing, and/or case reports: Hypoacusis (reversible), tinnitus (irreversible), vertigo

Contraindications

Hypersensitivity to plazomicin, any aminoglycoside, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving aminoglycosides; before therapy, inquire about previous hypersensitivity to other aminoglycosides. Discontinue plazomicin if an allergic reaction occurs.

• Nephrotoxicity: [US Boxed Warning]: May cause nephrotoxicity; risk factors include preexisting renal impairment, elderly patients, and concomitant nephrotoxic agents. Monitor renal function closely and reassess continuation of therapy if nephrotoxicity occurs. Most serum creatinine increases were ≤1 mg/dL above baseline and usually reversible; increases mainly occurred in patients with CrCl ≤90 mg/dL and were associated with plazomicin trough concentrations ≥3 mcg/mL.

• Neuromuscular blockade: [US Boxed Warning]: May cause neuromuscular blockade, especially in patients with underlying neuromuscular disorders and/or in patients receiving concomitant neuromuscular blocking agents.

• Ototoxicity: [US Boxed Warning]: May cause ototoxicity manifested as hearing loss, tinnitus, and/or vertigo; risk factors include family history of hearing loss, renal impairment, and receipt of higher doses and/or longer durations of therapy than recommended. Symptoms of ototoxicity may be irreversible and may not become evident until after therapy is complete.

• Superinfection: May cause superinfection of Clostridioides difficile infection (CDI) and pseudomembranous colitis; CDI has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hearing impairment: Use with caution in patients with hearing loss or a family history of hearing loss.

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.

• Renal impairment: Use with caution in patients with preexisting renal insufficiency; dosage modification required.

Special populations:

• Pregnancy: [US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

Metabolism/Transport Effects

None known.

Drug Interactions

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy

Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C: Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Risk C: Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor therapy

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Risk C: Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination

Kanamycin: Aminoglycosides may enhance the adverse/toxic effect of Kanamycin. Management: Coadministration of kanamycin and other potentially ototoxic or nephrotoxic agents, such as aminoglycosides, is not recommended. If this combination must be used, monitor carefully neurotoxic, ototoxic, or nephrotoxic effects. Risk D: Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Risk X: Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

Pregnancy Considerations

[US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Breast-Feeding Considerations

It is not known if plazomicin is present in breast milk.

As a class, aminoglycosides are expected to be poorly distributed into breast milk, limiting systemic exposure to a nursing infant. In general, modification of bowel flora may occur with any antibiotic exposure (Chung 2002). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine (prior to initiation of therapy and daily during therapy), plasma plazomicin trough (for patients with CrCl <90 mL/min); symptoms of ototoxicity or neuromuscular blockade

Reference Range

Trough <3 mcg/mL; measure plasma trough concentration within 30 minutes prior to second dose.

Mechanism of Action

Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit resulting in a defective bacterial cell membrane.

Pharmacodynamics and Pharmacokinetics

Distribution: 0.24 +/- 0.04 L/kg (Cass 2011)

Protein binding: ~20%

Half-life elimination: 3 to 4 hours (Cass 2011)

Time to peak: IV: At the end of or just after infusion (Cass 2011)

Excretion: Urine (97.5% as unchanged drug); feces (<0.2%); Clearance: 1.1 ± 0.1 mL/minute/kg (Cass 2011)

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Renal function impairment: AUC is increased and clearance is decreased in renal impairment.

Anti-infective considerations:

Parameters associated with efficacy: Gram-negative bacilli: Concentration-dependent; associated with AUC24/minimum inhibitory concentration (MIC); goal: ≥18 to 24 (bacteriostatic) or ≥73 to 85 (bactericidal; serious infections); AUC24: 210 to 315 mg•hour/L has been targeted for carbapenem-resistant Enterobacteriaceae (Kuti 2019; Noel 2019; Shaeer 2019).

Expected drug exposures in adults with normal renal function: AUC24: 15 mg/kg: ~225 to 265 mg•hour/L (Kuti 2019; Shaeer 2019; manufacturer's labeling).

Parameters associated with toxicity: Nephrotoxicity is associated with elevated Cmin (trough) concentrations (≥2 to 3 mg/L) (Shaeer 2019; manufacturer's labeling).

Postantibiotic effect: Bacterial killing continues after plazomicin concentration drops below the MIC of targeted pathogen; generally ~0.2 to 2.6 hours, though the actual time of postantibiotic effect varies with organism and plazomicin Cmax (peak) (Shaeer 2019; manufacturer's labeling).

Pricing: US

Solution (Zemdri Intravenous)

500 mg/10 mL (per mL): $37.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Zemdri (IN)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Asempa TE, Kuti JL, Seroogy JD, Komirenko AS, Nicolau DP. Application of the Hartford Hospital nomogram for plazomicin dosing interval selection in patients with complicated urinary tract infection. Antimicrob Agents Chemother. 2019;63(10):e00148-19. doi:10.1128/AAC.00148-19 [PubMed 31358580]
  2. Cass RT, Brooks CD, Havrilla NA, et al. Pharmacokinetics and safety of single and multiple doses of ACHN-490 injection administered intravenously in healthy subjects. Antimicrob Agents Chemother. 2011;55(12):5874-5880. [PubMed 21911572]
  3. Chung AM, Reed MD, Blumer JL. Antibiotics and breast-feeding: a critical review of the literature. Paediatr Drugs. 2002;4(12):817-837. [PubMed 12431134]
  4. Connolly LE, Riddle V, Cebrik D, Armstrong ES, Miller LG. A multicenter, randomized, double-blind, phase 2 study of the efficacy and safety of plazomicin compared with levofloxacin in the treatment of complicated urinary tract infection and acute pyelonephritis. Antimicrob Agents Chemother. 2018;62(4):e01989-17. doi:10.1128/AAC.01989-17 [PubMed 29378708]
  5. Hooton TM, Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 20, 2021.
  6. Kuti JL, Kim A, Cloutier DJ, Nicolau DP. Evaluation of plazomicin, tigecycline, and meropenem pharmacodynamic exposure against carbapenem-resistant enterobacteriaceae in patients with bloodstream infection or hospital-acquired/ventilator-associated pneumonia from the CARE study (ACHN-490-007). Infect Dis Ther. 2019;8(3):383-396. doi:10.1007/s40121-019-0251-4 [PubMed 31254273]
  7. Noel AR, Attwood M, Bowker KE, Kim A, Krause KM, MacGowan AP. Pharmacodynamics of plazomicin and a comparator aminoglycoside, amikacin, studied in an in vitro pharmacokinetic model of infection. Int J Antimicrob Agents. 2019;54(5):626-632. doi:10.1016/j.ijantimicag.2019.07.001 [PubMed 31299297]
  8. Pai MP, Rodvold KA. Aminoglycoside dosing in patients by kidney function and area under the curve: the Sawchuk-Zaske dosing method revisited in the era of obesity. Diagn Microbiol Infect Dis. 2014;78(2):178-187. doi:10.1016/j.diagmicrobio.2013.10.011 [PubMed 24268292]
  9. Quale J, Spelman D. Overview of carbapenemase-producing gram-negative bacilli. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 5, 2021.
  10. Shaeer KM, Zmarlicka MT, Chahine EB, Piccicacco N, Cho JC. Plazomicin: a next-generation aminoglycoside. Pharmacotherapy. 2019;39(1):77-93. doi:10.1002/phar.2203 [PubMed 30511766]
  11. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America guidance on the treatment of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2020 Oct 27:ciaa1478. doi:10.1093/cid/ciaa1478 [PubMed 33106864]
  12. Trang M, Seroogy JD, Van Wart SA, et al. Population pharmacokinetic analyses for plazomicin using pooled data from phase 1, 2, and 3 clinical studies. Antimicrob Agents Chemother. 2019;63(4):e02329-18. doi:10.1128/AAC.02329-18 [PubMed 30670433]
  13. Traynor AM, Nafziger AN, Bertino JS Jr. Aminoglycoside dosing weight correction factors for patients of various body sizes. Antimicrob Agents Chemother. 1995;39(2):545-548. doi: 10.1128/aac.39.2.545 [PubMed 7726530]
  14. Wagenlehner FME, Cloutier DJ, Komirenko AS, et al; EPIC Study Group. Once-daily plazomicin for complicated urinary tract infections. N Engl J Med. 2019;380(8):729-740. doi:10.1056/NEJMoa1801467 [PubMed 30786187]
  15. Zemdri (plazomicin) [prescribing information]. Warren, NJ: Cipla USA Inc; June 2020.
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